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Integrated single-cell profiling dissects cell-state-specific enhancer landscapes of human tumor infiltrating T cells.

Type: Epigenetics
Archiver: European Genome-phenome Archive (EGA)

1 Dataset 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001008662	Despite extensive studies on the chromatin landscape of exhausted T cells, the transcriptional wiring underlying functional and dysfunctional states of human tumor infiltrating lymphocytes (TILs) is incompletely understood. Here, we identify tissue-specific and general gene-regulatory landscapes in the wide breadth of CD8+ TIL functional states covering four cancer entities using single-cell chromatin profiling. We map enhancer-promoter interactions in human TILs by integrating single-cell chromatin accessibility with single-cell RNA-seq data from tumor entity-matching samples and prioritize key elements by super enhancer analysis. Our analysis reveals a human core chromatin trajectory to TIL dysfunction and identifies key enhancers, transcriptional regulators, and deregulated target genes involved in this process. Finally, we validate enhancer regulation at loci encoding PD1, TCF1, and TIM3 by targeting non-coding regulatory elements with potent CRISPR activators and repressors. In summary, our study advances the understanding of molecular regulation of TIL (dys-)function and provides a framework for modulating immunotherapeutic relevant TIL genes via their enhancers.	NextSeq 550	49

Publications	Citations
Atlas-guided discovery of transcription factors for T cell programming. Chung HK, Liu C, Battu A, Jambor AN, Pratt BM, Xie F, Riesenberg BP, Casillas E, Sun M, Landoni E, Li Y, Ye Q, Joo D, Green J, Syed Z, Brown NJ, Smith M, Ma S, Tan S, Chick B, Tripple V, Wang ZA, Wang J, Mcdonald B, He P, Yang Q, Chen T, Varanasi SK, LaPorta MA, Mann TH, Chen D, Hoffmann F, Ho J, Modliszewski J, Williams A, Liu Y, Wang Z, Liu J, Gao Y, Hu Z, Cho UH, Liu L, Wang Y, Hargreaves DC, Dotti G, Savoldo B, Thaxton JE, Milner JJ, Kaech SM, Wang W. Nature 651: 2026 1077-1087	1

Publications

Citations

Atlas-guided discovery of transcription factors for T cell programming.
Chung HK, Liu C, Battu A, Jambor AN, Pratt BM, Xie F, Riesenberg BP, Casillas E, Sun M, Landoni E, Li Y, Ye Q, Joo D, Green J, Syed Z, Brown NJ, Smith M, Ma S, Tan S, Chick B, Tripple V, Wang ZA, Wang J, Mcdonald B, He P, Yang Q, Chen T, Varanasi SK, LaPorta MA, Mann TH, Chen D, Hoffmann F, Ho J, Modliszewski J, Williams A, Liu Y, Wang Z, Liu J, Gao Y, Hu Z, Cho UH, Liu L, Wang Y, Hargreaves DC, Dotti G, Savoldo B, Thaxton JE, Milner JJ, Kaech SM, Wang W. Nature 651: 2026 1077-1087